Review Article

Integrin Signaling, Cell Survival, and Anoikis: Distinctions, Differences, and Differentiation

Figure 1

Intrinsic pathway of apoptosis. As decisional checkpoint of entry in apoptosis, Bcl-2 homologs perform functions—among many—in the integrity of the mitochondrion and thus regulating the formation of the apoptosome. Anti-apoptotic suppressor homologs inhibit their pro-apoptotic effector counterparts, preventing their translocation to the mitochondrion in order to create pores (and thus releasing cytochrome c and IAP inhibitors such as Smac/Diablo). Additional pro-apoptotic sensitizer and activator homologs act to inhibit the suppressors, although activators can furthermore interact with effectors to activate or enhance the functions of the latter. When the balance of Bcl-2 homologs is in favor of pro-apoptotics, effectors are free at the mitochondrion to homo-oligomerize, or hetero-oligomerize, with fellow effectors, and/or with activators, thus affecting the integrity of the mitochondrial membrane. APAF-1 and released cytochrome c can cooperate to dimerize pro-CASP-9, thus forming the apoptosome, resulting in massive CASP-9 activation and subsequent amplifying activation cascade of executioner caspases. Note that only the general outlines are shown here, for the sake of clarity. PARP, poly(ADP Ribose) polymerase; scissors: caspase-mediated cleavage.
738137.fig.001